Allele Genotype Research Articles

Correlation between LHCGR and NR5A1 genes polymorphism and male infertility risk

IntroductionInfertility is one of the important phenomena in human reproduction. Genetic factors are the most important cause of male infertility. Here, we aimed to investigate the correlation between idiopathic male infertility and SNPs of the LHCGR (rs2293275) and NR5A1 (rs1057517779) genes in the Iranian-Azeri population. MethodsThis case-control study consisted of 100 males with infertility and 100 healthy males from the Iranian Azeri population. Genomic DNA isolation from whole blood samples and Tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) method was used for genotyping. The data analysis was performed by chi-square (χ2) and Fisher’s exact tests. ResultsGenotyping analysis for LHCGR (rs2293275) polymorphism indicated that the frequency of C in the case group was significantly higher than in the control group (P < .05). Moreover, genotyping analysis for NR5A1 (rs1057517779) polymorphism indicated that the frequencies of the A allele and heterozygote GA genotype in the case group were significantly higher than those in the control group (P < .05). ConclusionOur study demonstrated that the SNPs of LHCGR (rs2293275) and NR5A1 (rs1057517779) genes may play a critical role in male infertility in the Iranian Azeri population. However, further studies on other ethnic origins with larger sample sizes are essential for accessing more accurate results. Moreover, functional experiments might be needed to understand the role of these polymorphisms in the molecular pathways involved in male fertility.

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism.

Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

Exploring the role of Sirtuin 3 gene polymorphisms and oxidative stress markers in the susceptibility to coronary artery disease.

Coronary artery disease (CAD) is a complex disorder influenced by genetic and environmental factors. This case-control study investigated the association between Sirtuin SIRT3 gene polymorphisms, serum malondialdehyde (MDA) levels, and CAD susceptibility. Blood samples were collected from 70 CAD cases and 30 controls at the Cardiac Center, Azadi Teaching Hospital, Duhok, Iraq. Genomic DNA was extracted, and PCR-based allele genotyping determined SIRT3 rs11246029 T/C polymorphisms. Serum MDA levels were measured using ELISA. Statistical analysis included t-tests, Mann-Whitney tests, and Spearman correlations. Odds ratios (OR) with 95% confidence intervals (CI) assessed genotypes/alleles and CAD associations. The accuracy of serum MDA in predicting the severity of CAD was evaluated using receiver operating characteristic (ROC) curve analysis. There were no significant variations in serum MDA levels between controls and CAD patients in the study. The diagnostic accuracy of serum MDA for CAD severity prediction was modest (Area Under Curve (AUC) = 0.56). Correlations revealed associations between MDA and total bilirubin (negative) and Troponin (positive). CRP correlated positively with LDH, glucose, cholesterol, LDL, CKmB, and Troponin. CKmB and Troponin are positively associated with clinical characteristics. Genotype analysis identified a significantly higher CAD risk with the CC genotype compared to controls. These findings shed light on the potential role of SIRT3 gene polymorphisms and serum MDA levels in CAD susceptibility. Further research is needed to understand underlying mechanisms and therapeutic implications based on these markers. 15092021-9-12. Registered 15 September 2021.

The association of rs1799983 eNOS gene polymorphism with dyslipidemia and efficacy of atorvastatin in correction of lipid exchange disorders in patients with diabetic nephropathy and essential hypertension

Objective — to search an association of rs1799983 endothelial nitric oxide synthase (eNOS) gene polymorphism with dyslipidemia (DLP) and the efficacy of atorvastatin used in correction of lipid exchange disorders in patients with diabetic nephropathy (DN) and essential hypertension (EH).&#x0D; Materials and methods. The study had been conducted in the clinical Department of Arterial Hypertension and Kidney Disease at L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 89 patients (pts) (43(48.3%) females and 46(51.7%) males) with DN of II—IV stages and EH of II—III stages aged 34 to 78 years old (an average age is 57.11±1.89 years old). They were also genotyped for rs1799983 eNOS gene polymorphism (G894T) with a use of polymerase chain reaction. GG genotype was revealed in 29(32.6%) of pts, GT genotype was found in 33(37.1%) of cases and 27(30.3%) participants of the study had TT genotype. With the use of immune enzyme method, serum levels of total cholesterol (TC), high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG) were measured in all included pts. Very low density lipoprotein cholesterol (VLDL‑C), low‑density lipoprotein cholesterol (LDL‑C), non‑HDL‑C and coefficient of atherogenicity were calculated by known formulas. Atorvastatin was prescribed to all the pts included in study for correction of lipid exchange disorders in daily doses of 10—20 mg (an average daily dose was 16.7±0.91 mg) for 24 weeks.&#x0D; Results. Rs1799983 eNOS gene polymorphism in pts with DN and EH was found to be associated with lipid parameters characterized a phenotype of diabetic DLP with its peculiar disorders in the systems of reverse cholesterol transport and lipoprotein lipolysis of TG‑containing VLDL. In this case a dominant G allele was associated with less significant lipid disorders than a recessive T allele. A homozygous state with allele G (genotype GG) in pts with DN and EH was associated with abnormalities in the system of TG‑containing VLDL lipolysis and an appearance of T allele in genotype (genotypes GT and TT) made an additional negative contribution to the state of lipid exchange and transport. In pts with genotype GT abnormalities in reverse cholesterol transport added to disorders in the system of TG‑containing VLDL lipolysis and in pts with genotype TT there was a combination of disorders in the systems of direct, reverse cholesterol transport and lipoprotein lipolysis. The study of hypolipidemic effects of atorvastatin depended on genotype of rs1799983 eNOS gene polymorphism showed that in GG genotype atorvastatin demonstrated mainly a hypocholesterolemic action while in genotypes contained T allele (GT and TT) we observed a reduction of hypocholesterolemic effect against the background of significant hypotriglyceridemic action and elevation of HDL‑C.&#x0D; Conclusions. In pts with DN and EH rs1799983 eNOS gene polymorphism was associated with diabetic DLP. A recessive allele T was associated with significant lipid disorders compared with a dominant G allele. A significant hypocholesterolemic effect of atorvastatin was observed in case of a presence of G allele in pts genotype while a presence of T allele in pts genotype (GT and TT) was associated with a reduction of atorvastatin cholesterol lowering action.&#x0D;

Isoniazid-induced liver injury risk level in different variants of N-acetyltransferase 2 (NAT2) polymorphisms: A literature review

Individual NAT2 genotype identity data should be enriched to prevent Isoniazid-induced liver injury (IDILI) and optimize the dose of Isoniazid (INH). Therefore, this study aims to present the level of IDILI risk for specific genotype alleles. The data collection involves literature indexed by Google Scholar, Scopus, and Pubmed databases. The search uses a combination of the following keyword variants “INH” OR “INH”, “liver injury” OR “hepatotoxicity”, “polymorphism” OR “pharmacogenomic”, and “N-acetyltransferase 2” OR “NAT2”. Furthermore, the screening results of library sources were narrowed to 11 original articles that met the inclusion criteria. The IDILI risk assessment analysis due to NAT2 enzyme polymorphism following the odds ratio has a 95% confidence interval. The results showed that the IDILI risk level of the slow acetylator group was 3.11 times higher than other populations. Meanwhile, the rapid and intermediate acetylator groups were not at risk. Three variants related to *6 allele were classified as high risk; *6A/*6A risk 5.76 times, *6A/*7B (5.54 times), and *6/*7 (4 times). The three allele configurations of the *5 and *7 were also classified as a risk; *5B/*7B (5 times), *7B/*7B (3.23 times), and *5/*7 (2,74 times).

Association of genetic variations in FoxP3 gene with Graves' disease in a Southwest Chinese Han population.

Graves' disease (GD) is a T cell-mediated organ-specific autoimmune disease. Forkhead box P3 (FoxP3) is an excellent marker for the induction and development of regulatory T cells (Tregs). Recent studies showed that single-nucleotide polymorphisms (SNPs) in the FoxP3 gene were associated with the increased susceptibility to several autoimmune diseases. In the present study, we investigated the association of FoxP3 gene polymorphisms with GD in a Southwest Chinese Han population. A two-stage case-control study was performed in 890 healthy controls (male, 282; female, 608) and 503 patients with GD (male, 138; female, 365). Four SNPs (rs3761548, rs3761549, rs3761547, and rs2280883) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism assay. The χ2 test was used to compare the genotype distributions and allele frequencies between GD patients and healthy controls. In the first stage, the significantly increased frequencies of the A allele (p = .031, odds ratio [OR] = 1.635) and AA genotype (p = .023, OR = 3.257), together with a significantly decreased frequency of the C allele (p = .031, OR = 0.611) of FoxP3/rs3761548 were found in female patients with GD. None of the other FoxP3 SNPs was associated with GD susceptibility. Subsequent validation and combination of data confirmed the association between FoxP3/rs3761548 and the female patients with GD (A allele: p < .001, OR = 1.672; AA genotype: p = .005, OR = 2.488; CC genotype: p = .001, OR = 0.622; C allele: p < .001, OR = 0.615, respectively). Our findings suggest that FoxP3/rs3761548 is significantly associated with female GD patients in a Southwest Chinese Han population.

Polymorphism of cytokine and C-reactive protein genes in patients with psoriasis in the Kemerovo region of Russia

Aim. To study the associations of polymorphisms of IL-1b (rs16944), IL-6 (rs1554606), IL-8 (rs2227306), IL-10 (rs1800896), TNFα (rs361525), CRP (rs1205) genes and their intergenic interactions with the risk of psoriasis development in Kemerovo region residents. Materials and Methods. We examined 170 patients (102 men and 78 women) a clinically established diagnosis of vulgar psoriasis. The average age of patients was 46.2+3.9 years, 165 people (97%) had progressive stage psoriasis. The control group (n=155) included 98 healthy men and 57 women matched by age. Genomic DNA isolated from peripheral blood leukocytes by phenol-chloroform extraction according to the standard protocol was used as material. Logistic regression analysis was performed to assess the role of intergenic interactions in the development of psoriasis. Conclusion. In patients of the Kemerovo region, vulgar psoriasis is associated with minor homozygous genotypes of polymorphic variants of TNFα (rs361525), IL-1b (rs16944), CRP (rs1205) genes. The minor homozygous TNFα (rs361525) genotype has a high odds ratio and is determinant in the development of this form of psoriasis among all genes studied. The major allele and IL-10 genotype (rs1800896) is a disease modifier and affects the clinical course, particularly the development of inflammatory plaques and papules on the lower and upper extremities of patients.

Association between interleukin-12B gene polymorphisms and multiple sclerosis in turkish population

Elevated levels of IL-12p40 have been observed in the cerebrospinal fluid and serum of MS patients, and it has been suggested that genetic variants in the IL-12B gene may contribute to MS susceptibility and/or pathogenesis. In this study, we investigated the association between MS and IL-12B gene rs17860508 and rs3212227 polymorphisms in the Turkish population. We identified two polymorphic regions in the IL-12B gene using bioinformatics tools and genotyped 351 MS patients and 221 healthy controls for these variants. Our results showed a significant association between the IL-12B rs17860508 polymorphism and MS, but no significant relationship between rs17860508 genotype distribution and allele frequency and MS age onset or subtypes. Genotype distribution and allele frequency of IL-12B rs3212227 polymorphism did not show any significant association with MS directly. However, AC genotype of IL-12B rs3212227 polymorphism in early-onset multiple sclerosis (EOMS) was a risk factor according to age of onset. Additionally, we observed a higher risk for the relapsing-remitting multiple sclerosis (RRMS) subtype in females. This is the first study to investigate the association between IL-12B polymorphisms and MS in the Turkish population.

Allelic frequency of beta-lactoglobulin gene in different cattle breeds

The results of research on the frequency of genotypes AA, AB, BB and alleles A and B of milk protein beta-lactoglobulin in various cattle breeds over the past decades were presented and summarized. The livestock of the following foreign countries was considered: Italy, India and the Czech Republic. Also, on the territory of the Russian Federation, breeding stock and sires of the Republic of Bashkortostan, Tatarstan, Pskov, Samara and Arkhangelsk regions, as well as sires in the Altai Territory, were studied. Black-and-White breed is the most studied one. Moreover, there are data on the Simmental and Kholmogory breeds of cattle. The frequency of allele B among the breeding stock of Black-and-White breed in farms ranged from 0.21 to 0.64. The frequency of allele B among the breeding stock of Simmental breed in farms ranged from 0.42 to 0.65. The frequency of allele B among the breeding stock of Kholmogory breed in farms was from 0.60 to 0.70. The frequency of allele B among sires of Black-and-White breed ranged from 0.43 to 0.69. In most farms, BB genotype leads in terms of quality indicators of milk productivity, and AB genotype leads in quantitative indicators of milk productivity. However, in some farms, AA genotype prevails in terms of milk yield and protein, and this genotype is also associated with a high content of dry skimmed milk residue and resistance to mastitis. Thus, further in-depth study of the beta-lactoglobulin gene is necessary, since new data will expand the understanding of the effect of this gene on economically useful traits of animals and will eliminate contradictions in the available data.

Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes

BackgroundThe biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly.ObjectiveThis retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR).MethodsWe analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR.ResultsAmong the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014).ConclusionOxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.

Single nucleotide polymorphism of osteoprotegerin as a possible biomarker of rheumatoid arthritis in Bashkir population of Chelyabinsk region

Rheumatoid arthritis (RA) is a multifactorial autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis. The protein osteoprotegerin (OPG) is a member of bone tissue homeostasis (RANK/RANKL/OPG) which is responsible for the regulation of osteoclast differentiation and osteolysis. The altered binding of RANKL and OPG is one of the causes of many diseases with increased production of pro-inflammatory cytokines, including rheumatoid arthritis. Polymorphic variants of the genes that control protective reactions could affect the level of production for encoded proteins and, thus, changing the course of immune response in RA. G1181C SNP in osteoprotegerin gene leads to disruption of its transcriptional activity and conformation of the protein itself, which can lead to an imbalance of pro- and anti-inflammatory cytokines. We analyzed the relationship between the TNFRSF11B gene polymorphism at the 1181 G C position and the risk of developing RA in the Bashkir population. The analysis was based on a molecular genetic study of single nucleotide polymorphism in groups of patients with rheumatoid arthritis and conditionally healthy individuals of the Bashkir population of the Chelyabinsk Region. Statistical evaluation was carried out using standard criteria generally accepted in immunogenetics. The 1181*GC polymorphism of the osteoprotegerin gene is characterized by interpopulation differences, which confirms the importance of using an ethnically identical comparison group to assess the association with a predisposition to multifactorial pathology. We showed that the carriage of genotype 1181 G/C was increased in the group of Bashkirs with rheumatoid arthritis. This genotype could be considered a biomarker of susceptibility to RA. No differences in the SNP allelic frequencies and genotypes were found among women with RA. Our research is a part of comprehensive assessment of the interaction of cytokines and their receptors from the TNFαsuperfamily as an immunogenetic component of RA genesis.

Endothelin-1 Gene Polymorphism in Chronic Obstructive Pulmonary Disease: A Case-Control Study

Abstract&#x0D; Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common multifactorial disease which has heterogeneous pathogenesis. The most important risk factor is smoking. In addition to many pathogenic mechanisms taking part in inflammatory process, Our study group does research on the relation of COPD with single nucleotide gene polymorphism at ET-1 gene. In the current studies there being a high ratio of Endotelin-1 (ET-1) in BAL liquid of COPD cases made researchers think ET-1 may have an important role in pathogenesis of COPD. &#x0D; Methods: This prospective case-control study included 89 patients admitted with COPD and 87 control patients. In our study, we search for the density of single nucleotide gene polymorphism (+134 insA/delA) in ET-1 gene in the 87 smoking COPD and 89 healthy cases. Allele ratio and genotype distribution, distribution amongst three genotype in the COPD patient and healthy control group was analyzed. In this study, for endothelin gene -3A/-4A (-138 insertion/deletion) polymorphism analysis, PCR-RFLP method was used. &#x0D; Results: In comparison with the healthy group, the COPD group has higher ratio of ET-1 gene (+134 insA/delA) polymorphism (p&lt; 0,001). &#x0D; Conclusion: Endotelin-1 gene polymorphism (+134 insA/delA) significantly increased in the patients than healthy ones (p

Genotypic and phenotypic insights into virulence factors of nosocomial Stenotrophomonas maltophilia isolates collected in Bulgaria (2011-2022).

The present study aimed to explore the virulence characteristics in 221 Bulgarian nosocomial Stenotrophomonas maltophilia isolates (2011-2022) via screening for the presence of virulence genes, their mutational variability, and the corresponding enzyme activity. PCR amplification, enzymatic assays, whole-genome sequencing (WGS), and biofilm quantification on a polystyrene plate were performed. The incidence of virulence determinants was as follows: stmPr1 (encoding for the major extracellular protease StmPr1) 87.3%, stmPr2 (minor extracellular protease StmPr2) 99.1%, Smlt3773 locus (outer membrane esterase) 98.2%, plcN1 (non-hemolytic phospholipase C) 99.1%, and smf-1 (type-1 fimbriae, biofilm-related gene) 96.4%. The 1621-bp allele of stmPr1 was most frequently found (61.1%), followed by the combined allelic variant (17.6%), stmPr1-negative genotype (12.7%), and 868-bp allele (8.6%). Protease, esterase, and lecithinase activity was observed in 95%, 98.2%, and 17.2% of the isolates, respectively. The WGS-subjected isolates (n = 9) formed two groups. Five isolates possessed only the 1621-bp variant of stmPr1, higher biofilm formation ability (Optical Density at λ = 550 nm (OD550): 1.253-1.789), as well as a low number of mutations in the protease genes and smf-1. Three other isolates had only the 868-bp variant, weaker biofilm production (OD550: 0.788-1.108), and higher number of mutations within these genes. The only weak biofilm producer (OD550 = 0.177) had no stmPr1 alleles. In conclusion, the similar PCR detection rates did not allow differentiation of the isolates. In contrast, WGS permitted stmPr1 alleles-based differentiation. To the best of our knowledge, this is the first Bulgarian study presenting genotypic and phenotypic insights into virulence factors of S. maltophilia isolates.

Dose effects of restorer gene modulate pollen fertility in cotton CMS-D2 restorer lines via auxin signaling and flavonoid biosynthesis.

Dose effects of Rf1 gene regulated retrieval mechanism of pollen fertility for CMS-D2 cotton. Cytoplasmic male sterility conditioned by Gossypium harknessii cytoplasm (CMS-D2) is an economical pollination control system for producing hybrid cotton seeds compared to artificial and chemical emasculation methods. However, the unstable restoring ability of restorer lines is a main barrier in the large-scale application of "three-line" hybrid cotton in China. Our phenotypic investigation determined that the homozygous Rf1Rf1 allelic genotype had a stronger ability to generate fertile pollen than the heterozygous Rf1rf1 allelic genotype. To decipher the genetic mechanisms that control the differential levels of pollen fertility, an integrated metabolomic and transcriptomic analysis was performed at two environments using pollen grains of four cotton genotypes differing in Rf1 alleles or cytoplasm. Totally 5,391 differential metabolite features were detected, and 369 specific differential metabolites (DMs) were identified between homozygous and heterozygous Rf1 allelic genotypes with CMS-D2 cytoplasm. In addition, transcriptome analysis identified 2,490 differentially expressed genes (DEGs) and 96 unique hub DEGs with dynamic regulation in this comparative combination. Further integrated analyses revealed that several key DEGs and DMs involved in indole biosynthesis, flavonoid biosynthesis, and sugar metabolism had strong network linkage with fertility restoration. In vitro application of auxin analogue NAA and inhibitor Auxinole confirmed that over-activated auxin signaling might inhibit pollen development, whereas suppressing auxin signaling partially promoted pollen development in CMS-D2 cotton. Our results provide new insight into how the dosage effects of the Rf1 gene regulate pollen fertility of CMS-D2 cotton.

Allele frequency and genotype distribution of the opioid receptor μ-1 (OPRM1) A118G polymorphism in the Western Saudi population.

The single nucleotide polymorphism (SNP) A118G (rs1799971) in the Mu Opioid Receptor 1 (OPRM1) gene is associated with significant variations in analgesic doses and adverse effects of opioids. The A118G OPRM1 allele distributions vary significantly between different populations worldwide. The study aimed to assess the allele frequency and genotype distribution of OPRM1 A118G SNP in Saudis. This cross-sectional study included 124 healthy Saudis (62 males and 62 females) visiting the King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The Oragene®-DISCOVER (OGR-600) kits were used to collect saliva samples from the participants. Polymerase chain reaction-restriction fragment length polymorphism was utilized to assess the SNP. Among the tested population, 79.03% (95% C.I. 70.81-85.82) were homozygous wild-type A118A, 16.13% (95% C.I. 10.14-23.80) were heterozygous A118G, and 4.84% (95% C.I. 1.80-10.23) were homozygous mutant G118G. OPRM1 A118G polymorphism allele frequencies were 87% (95% C.I. 79.89-92.44) and 13% (95% C.I. 7.56-20.11) for the 118A and 118G alleles, respectively. A higher frequency of the OPRM1 118G allele was present in females, 21% (95% C.I. 11.66-33.17) compared to males, 5% (95% C.I. 1.01-13.50). Relative to other Asian countries, the Saudi population showed a low prevalence of the OPRM1 A118G polymorphism, with a higher frequency of the 118G allele in females. Our research will contribute to the existing knowledge on the prevalence of OPRM1 A118G polymorphism, which could be considered for the personalized prescribing of opioid analgesics.

Allelic variants of CYP2B6 gene expression and its implication on the pathogenesis of malaria among a cohort of outpatients in North-Central Nigeria

Abstract Background Human cytochrome P450 2B6 (CYP2B6) is fortified with the biotransformation of the antimalarial, artemisinin combination therapy (ACT). Owing to emerging reports of Plasmodium species resistance to ACT in other climes, CYP2B6*6 genotype significantly alters ACT metabolism. In North-Central Nigeria, the distribution of the CYP2B6*6 variant is poorly documented. This study investigated the distribution of CYP2B6 c.516G&gt;T variants and its relationship with certain malaria pathogenesis among a cohort of clinical-malaria outpatients in Ilorin, Nigeria. Methods A total of 50 symptomatic P. falciparum malaria-positive samples were genotyped for CYP2B6 c.516G&gt;T using restriction fragment length polymorphism and a specific haplotype population was established. The allele frequencies and genotype distributions were analyzed. Haplotypes were clustered using Ward’s method. Correlations determined include defective CYP2B6 versus parasitemia densities and thrombocytopenia, respectively. Results Forty-five samples show genotypic ratios and nine CYP2B6 genetic single nucleotide polymorphisms were identified. The following haplotypes (64C&gt;T = *1/*2, 785A&gt;G = *1/*4, and 1459C&gt;T = *1/*5) occurred and *2, *3, and *18 alleles harbor 64C&gt;T, 777C&gt;A, −82T&gt;C, and 499C&gt;G. The codon 64CT, 516GT, and 785AG; −82TC and 777CA; and 499CG, 516GT, and 785AG were identified as *2/*6 heterozygotes. Samples with 516GT and 785GG genotypes occurred with *4/*6 heterozygotes. Mutant trait alleles recorded high parasitemia 72 h post-ACT regimen. Only individuals with CYP2B6*6 alleles had severe malaria and thrombocytopenia. Conclusion This report contributes to the growing knowledge of CYP2B6*6 genotype frequency and its relationship with malaria pathogenesis among a Nigerian population.

Effects of prophylactic red blood cell (RBC) transfusion with extended antigen matching on alloimmunization in patients with Sickle Cell Disease (SCD)

BackgroundRBC alloimmunization remains a significant problem for many patients with SCD. To reduce alloimmunization some strategies have been implemented to provide limited or extended antigen matched RBC transfusions to patients with SCD who need chronic transfusion support. The aim of this study was to evaluate the effects of prophylactic RBC transfusion with extended antigen matching on alloimmunization in patients with SCD. MethodsThis is a 20-year retrospective study of patients with SCD transfused with RBCS that were prospectively matched for D, C, c, E, e, K, Fya/Fyb, Jka/Jkb and S antigens. Our study included 95 patients, and none had antibodies documented before their first transfusion. Patients and donors were phenotyped and molecular typing was performed in all patients who had recent transfusions or a positive direct antiglobulin test to predict their antigen profile. Unexpected antibodies to the Rh system, meaning anti-Rh antibodies in patients whose serologic phenotype was Rh positive, were investigated by molecular genotyping for RH variant alleles. ResultsDuring this study-period, 12 (12.6%) were alloimmunized and 83 (87.4%) were not. Among the 12 patients who alloimmunized, 7 (58.3%) developed antibodies to Rh antigens and 5 (41.7%) produced antibodies to low prevalence antigens. All patients who developed Rh antibodies had RH variant alleles. Autoantibodies were found in 16 (16.8%) transfused patients. ConclusionSCD patients benefit from receiving prophylactic RBC transfusions with extended antigen matching, as demonstrated by the reduction on the rates of alloimmunization and the lack of antibodies to K, FY, JK and S antigens, however, this strategy does not avoid alloimmunization to Rh and low-prevalence antigens.

The Role of SNAP-25 in Autism Spectrum Disorders Onset Patterns.

Autism spectrum disorders (ASD) can present with different onset and timing of symptom development; children may manifest symptoms early in their first year of life, i.e., early onset (EO-ASD), or may lose already achieved skills during their second year of life, thus showing a regressive-type onset (RO-ASD). It is still controversial whether regression represents a neurobiological subtype of ASD, resulting from distinct genetic and environmental causes. We focused this study on the 25 kD synaptosomal-associated protein (SNAP-25) gene involved in both post-synaptic formation and adhesion and considered a key player in the pathogenesis of ASD. To this end, four single nucleotide polymorphisms (SNPs) of the SNAP-25 gene, rs363050, rs363039, rs363043, and rs1051312, already known to be involved in neurodevelopmental and psychiatric disorders, were analyzed in a cohort of 69 children with EO-ASD and 58 children with RO-ASD. Both the rs363039 G allele and GG genotype were significantly more frequently carried by patients with EO-ASD than those with RO-ASD and healthy controls (HC). On the contrary, the rs1051312 T allele and TT genotype were more frequent in individuals with RO-ASD than those with EO-ASD and HC. Thus, two different SNAP-25 alleles/genotypes seem to discriminate between EO-ASD and RO-ASD. Notably, rs1051312 is located in the 3' untranslated region (UTR) of the gene and is the target of microRNA (miRNA) regulation, suggesting a possible epigenetic role in the onset of regressive autism. These SNPs, by discriminating two different onset patterns, may represent diagnostic biomarkers of ASD and may provide insight into the different biological mechanisms towards the development of better tailored therapeutic and rehabilitative approaches.

Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia

BackgroundPlasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb) < 5.0 g/dL in children] is the most common clinical manifestation of severe malaria in such regions. Although innate immune response genes are known to influence the development of SMA, the role of natural killer (NK) cells in malaria pathogenesis remains largely undefined. As such, we examined the impact of genetic variation in the gene encoding a primary NK cell receptor, natural cytotoxicity-triggering receptor 3 (NCR3), on the occurrence of malaria and SMA episodes over time.MethodsSusceptibility to malaria, SMA, and all-cause mortality was determined in carriers of NCR3 genetic variants (i.e., rs2736191:C > G and rs11575837:C > T) and their haplotypes. The prospective observational study was conducted over a 36 mos. follow-up period in a cohort of children (n = 1,515, aged 1.9–40 mos.) residing in a holoendemic P. falciparum transmission region, Siaya, Kenya.ResultsPoisson regression modeling, controlling for anemia-promoting covariates, revealed a significantly increased risk of malaria in carriers of the homozygous mutant allele genotype (TT) for rs11575837 after multiple test correction [Incidence rate ratio (IRR) = 1.540, 95% CI = 1.114–2.129, P = 0.009]. Increased risk of SMA was observed for rs2736191 in children who inherited the CG genotype (IRR = 1.269, 95% CI = 1.009–1.597, P = 0.041) and in the additive model (presence of 1 or 2 copies) (IRR = 1.198, 95% CI = 1.030–1.393, P = 0.019), but was not significant after multiple test correction. Modeling of the haplotypes revealed that the CC haplotype had a significant additive effect for protection against SMA (i.e., reduced risk for development of SMA) after multiple test correction (IRR = 0.823, 95% CI = 0.711–0.952, P = 0.009). Although increased susceptibility to SMA was present in carriers of the GC haplotype (IRR = 1.276, 95% CI = 1.030–1.581, P = 0.026) with an additive effect (IRR = 1.182, 95% CI = 1.018–1.372, P = 0.029), the results did not remain significant after multiple test correction. None of the NCR3 genotypes or haplotypes were associated with all-cause mortality.ConclusionsVariation in NCR3 alters susceptibility to malaria and SMA during the acquisition of naturally-acquired malarial immunity. These results highlight the importance of NK cells in the innate immune response to malaria.

IL-10 (−1082 G/A) polymorphism in Bataknese with schizophrenia

ObjectivesThree biallelic polymorphisms at the promoter region of the interleukin-10 (IL-10) gene have been associated with susceptibility to schizophrenia. The aim of this case-control study was to investigate the association between IL-10 (−1082) G/A gene polymorphisms and schizophrenia among Bataknese, a native tribe inhabiting the North Sumatera province in Indonesia. MethodsA total of 194 unrelated participants (n = 97 for each case and control groups) participated in this study. Polymerase chain reaction restriction fragment length polymorphism molecular genotyping was conducted to assess the genotype and allele distribution of IL-10 (−1082 G/A). ResultsAllele variations indicated that the dominant allele in the Batak tribe was allele A, whereas homozygous GG genotypes were not found in either group. The A allele and AA genotype were found to be risk factors for developing schizophrenia (OR = 2.26, 95% CI = 1.1825–4.3559 and OR = 2.56, 95% CI = 1.280–5.152, respectively). ConclusionOnly the A allele and AA genotype of the IL-10 gene polymorphism at −1082 G/A contribute to schizophrenia susceptibility in Bataknese.